Normal cats (Felis catus), and cats with Gm2 gangliosidosis associated with beta-hexosaminidase deficiency, will be utilized in experiments aimed at exploring possible strategies for enzyme replacement therapy in human Gm2 gangliosidosis. Characterization of beta-hexosaminidase in normal cats by biochemical and immunological methods, and similar studies in diseased animals, will be carried out to establish the validity of the cat with Gm2 gangliosidosis as a model for the human disease. Different beta-hexosamidase forms isolated from human placenta and plasma will be injected in normal cats; plasma clearance, organ disposition and subcellular location of the exogenous enzymes will be determined by a combination of biochemical, electrophoretic and immunological methods. Recognition and uptake mechanisms of the feline liver, and endocellular survival of exogenous beta-hexosaminidase, will be studied to aid in the formulation of organ-targeting procedures, and to assess the usefulness of different human enzyme forms in enzyme replacement therapy. Intermittent hyperbaric oxygenation will be administered to normal cats as possible means of inducing permeability of the blood-brain barrier to exogenous human beta-hexosaminidase. The possible therapeutic value of regimens combining hyperbaric oxygen treatments and human beta-hexosaminidase injection will be assessed biochemically, by their effect on Gm2 ganglioside storage in the brain of diseased cats, and clinically, by their effect on delaying the onset of symptoms in enzyme-deficient animals identified and treated in the first weeks of life.